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Prostate Cancer Prevention (PDQ®)

Significance

Incidence and Mortality

Carcinoma of the prostate is the most common tumor in men in the United States, with an estimated 220,800 new cases and 27,540 deaths expected in 2015.[1] A wide range of estimates of the impact of the disease are notable. The disease is histologically evident in as many as 34% of men in their fifth decade and in up to 70% of men aged 80 years and older.[2,3] Prostate cancer will be diagnosed in almost one-fifth of U.S. men compared with about 3% of men who will be expected to die of the disease.[4] The estimated reduction in life expectancy of men who die of prostate cancer is approximately 9 years.[5]

The extraordinarily high rate of clinically occult prostate cancer in the general population compared with the 20-fold lower likelihood of death from the disease indicates that many of these cancers have low biologic risk. Concordant with this observation are the many series of patients with lower-risk (i.e., Gleason 6 and some low-volume Gleason 7 tumors) prostate cancer managed by surveillance alone with high survival rates at 5 and 10 years of follow-up.[6] Data demonstrate, however, that with longer follow-up, higher-grade cancers are associated with a greater risk of prostate cancer death.[7,8]

Because of marked variability in tumor differentiation from one microscopic field to another, many pathologists will report the range of differentiation among the malignant cells that are present in a biopsy using the Gleason grading system. This grading system includes five histologic patterns distinguished by the glandular architecture of the cancer. The architectural patterns are identified and assigned a grade from 1 to 5 with 1 being the most differentiated and 5 being the least differentiated. The sum of the grades of the predominant and next most prevalent will range from 2 (well-differentiated tumors) to 10 (undifferentiated tumors).[9,10] Systematic changes to the histological interpretation of biopsy specimens by anatomical pathologists have occurred during the prostate-specific antigen (PSA) screening era (i.e., since about 1985) in the United States.[11] This phenomenon, sometimes called “grade inflation,” is the apparent increase in the distribution of high-grade tumors in the population for a period of time but in the absence of a true biological or clinical change. It is possibly the result of an increasing tendency for pathologists to read tumor grade as more aggressive, resulting in a higher preponderance to treat these cancers aggressively.[12]

Treatment options available for prostate cancer include radical prostatectomy, external-beam radiation therapy, brachytherapy, cryotherapy, focal ablation, androgen deprivation with luteinizing hormone-releasing hormone analogs and/or antiandrogens, intermittent androgen deprivation, cytotoxic agents, and active surveillance. Of all the means of management, only radical prostatectomy has been tested in a randomized clinical trial to assess survival benefit. In this study, prostatectomy was found to be superior to surveillance in men with localized prostate cancer in terms of reduced rates of metastases (relative hazard [RH] = 0.63; 95% confidence interval [CI], 0.41–0.96) and disease specific (RH = 0.5; 95% CI, 0.27–0.91) and overall mortalities.[13] The relative efficacy of radical prostatectomy to the other forms of treatment has not been adequately addressed.[14] Confounding issues in the treatment of prostate cancer include side effects with treatment, inability to predict the natural history of a given cancer, patient comorbidity that may affect an individual’s likelihood of surviving long enough to be at risk for disease morbidity and mortality, and an increasing body of evidence suggesting that with careful PSA monitoring following treatment, a substantial fraction of patients may suffer disease recurrence .[15]

Because of considerable uncertainty regarding the efficacy of treatment and the difficulty with selecting patients for whom there is a known risk of disease progression, opinion in the medical community is divided regarding screening for carcinoma of the prostate. While both digital rectal examination and PSA screening have demonstrated reasonable performance characteristics (sensitivity, specificity, and positive predictive value) for the early detection of prostate cancer, conflicting outcomes of randomized trials examining the impact of screening on mortality has led to some organizations to recommend for and others to recommend against screening.[16,17]

The tremendous impact of prostate cancer on the U.S. population and the financial burden of the disease for both patients and society have led to an increased interest in primary disease prevention.